United States Patent 6,495,164: Preparation of Injectable Suspensions Having Improved Injectability
Overview of the Patent
United States Patent 6,495,164, titled "Preparation of Injectable Suspensions Having Improved Injectability," addresses a significant issue in the pharmaceutical industry related to the formulation and administration of injectable suspensions. This patent, granted on December 17, 2002, presents a novel approach to enhancing the injectability of suspensions, particularly those containing microparticles.
Background and Motivation
Traditionally, the preparation of injectable suspensions has been challenging due to issues related to viscosity, particle size, and the ability to wet and suspend microparticles evenly. Conventional wisdom suggested that increasing the viscosity of the fluid phase would hinder injectability and syringeability. However, the inventors of this patent discovered that, contrary to conventional teachings, increasing the viscosity of the fluid phase can actually improve injectability and reduce in vivo injectability failures[1].
Key Claims and Innovations
Improved Viscosity
The patent claims that by increasing the viscosity of the fluid phase of an injectable suspension, the injectability is improved. This is achieved despite the fact that viscous vehicles are generally not optimal for preparing homogeneous suspensions of microparticles due to their inability to penetrate and wet out a mass of dry particles effectively[1].
Suspension Preparation
The invention involves preparing suspensions where microparticles are suspended in an injection vehicle with suitable wetting characteristics. This ensures that the microparticles are evenly distributed and do not clump irreversibly, which is a common issue with viscous suspensions[1].
Manufacturing Process
The patent describes a detailed manufacturing process for preparing these suspensions. For example, risperidone microparticles were manufactured at different scales (125 gm and 1 Kg) using a process similar to that described in U.S. Pat. No. 5,792,477. The microparticles were then transferred into glass vials and capped with a Teflon-lined septum[1].
Injection Testing
The patent outlines a method for testing the injectability of these suspensions. This involves using a syringe and needle to inject the suspension through different sieve mesh sizes to determine the optimal conditions for successful injection without clogging the needle[1].
Technical Details
Particle Size and Distribution
The patent specifies that the microparticles had similar particle sizes, ranging from a Mass Median Diameter of 91 μm to 121 μm, based on Hyac-Royco analysis. This uniformity is crucial for ensuring consistent injectability[1].
Viscosity and Wetting Characteristics
The invention emphasizes the importance of the viscosity and wetting characteristics of the injection vehicle. The vehicle must be able to wet and suspend the microparticles effectively, which is a critical factor in preventing clumping and ensuring smooth injection[1].
Patent Landscape
Related Patents
The patent references other related patents, such as U.S. Pat. No. 5,792,477 and U.S. Pat. No. 5,922,253, which provide additional context and methodologies for preparing microparticles and injectable suspensions[1][2].
International Patent System
The patent is part of a broader international patent landscape. Tools like the Global Dossier and Common Citation Document (CCD) facilitate the search and analysis of related patent applications across different intellectual property offices, including the USPTO, EPO, JPO, and WIPO[4].
Economic and Practical Impact
Pharmaceutical Industry
This patent has significant implications for the pharmaceutical industry, particularly in the development and administration of injectable medications. By improving the injectability of suspensions, it enhances patient safety and compliance, and reduces the risk of in vivo injectability failures[1].
Research and Development
The innovative approach outlined in this patent can inspire further research and development in the field of pharmaceutical formulations. It challenges conventional wisdom and provides a new paradigm for formulating injectable suspensions, which can lead to the development of more effective and safer medications.
Challenges and Limitations
Viscous Vehicles
Despite the improvements, the use of viscous vehicles still poses challenges, such as the difficulty in transferring the suspension from the vial to the syringe and the potential for clumping if the wetting characteristics are not optimal[1].
Scalability
The patent describes manufacturing processes at different scales, but scalability remains a challenge. Ensuring consistent quality and injectability across large-scale production is crucial for commercial viability.
Future Directions
Advanced Formulations
Future research could focus on developing advanced formulations that further enhance the wetting characteristics and viscosity of the injection vehicle, potentially leading to even better injectability and stability of the suspensions.
Combination Therapies
The improved injectability of suspensions could also facilitate the development of combination therapies where multiple active agents are suspended in a single vehicle, enhancing treatment efficacy and patient convenience.
Key Takeaways
- Improved Injectability: Increasing the viscosity of the fluid phase can improve the injectability of suspensions.
- Optimal Wetting Characteristics: The injection vehicle must have suitable wetting characteristics to prevent clumping and ensure even distribution of microparticles.
- Scalability: Consistent quality and injectability must be maintained across different scales of production.
- Pharmaceutical Impact: This patent enhances patient safety and compliance by reducing in vivo injectability failures.
- Future Research: Advanced formulations and combination therapies are potential areas for future development.
FAQs
Q: What is the main innovation of United States Patent 6,495,164?
A: The main innovation is the discovery that increasing the viscosity of the fluid phase of an injectable suspension can improve injectability, contrary to conventional teachings.
Q: What are the challenges associated with using viscous vehicles in injectable suspensions?
A: The challenges include the difficulty in transferring the suspension from the vial to the syringe and the potential for clumping if the wetting characteristics are not optimal.
Q: How does the patent address the issue of particle size and distribution?
A: The patent specifies that the microparticles should have uniform sizes, ranging from a Mass Median Diameter of 91 μm to 121 μm, to ensure consistent injectability.
Q: What is the significance of the Global Dossier and CCD in the context of this patent?
A: These tools facilitate the search and analysis of related patent applications across different intellectual property offices, enhancing the global patent landscape.
Q: What are the potential future directions for research based on this patent?
A: Future research could focus on developing advanced formulations with better wetting characteristics and viscosity, as well as exploring combination therapies.
Sources
- US6495164B1 - Preparation of injectable suspensions having improved injectability - Google Patents
- US6495164B1 - Preparation of injectable suspensions having ... - Google Patents
- Patent Claims Research Dataset - USPTO
- Search for patents - USPTO - USPTO
- US-20080044478-A1 - Unified Patents Portal - Unified Patents Portal
